(ChemotherapyAdvisor) – Minimal residual disease (MRD) levels were an independent predictor of progression-free and overall survival in patients with chronic lymphocytic leukemia (CLL) treated with fludarabine and cyclophosphamide (FC) or FC plus rituximab (FCR), according to results of a multivariate analysis from the German CLL Study Group CLL8 trial published in the Journal of Clinical Oncology online February 13.
These data suggest quantification of MRD “might serve as a surrogate marker to assess treatment efficacy in randomized trials before clinical end points can be evaluated,” the investigators wrote.
Levels of MRD were prospectively quantified in 1,775 blood and bone marrow samples from 493 patients, who were categorized into low- (<10-4), intermediate- (≥10-4 to <10-2), and high-level (≥10-2) groups.
During and after treatment with FC or FCR, low MRD levels were found to be associated with longer progression-free survival (PFS) and overall survival (P<0.0001). When assessed two months after therapy, low levels of MRD were associated with an estimated median PFS of 68.7 months; intermediate and high MRD levels were associated with a median PFS of 40.5 and 15.4 months, respectively, as well as greater risk of disease progression: HR=2.49 and HR=14.7 vs. low levels.
Patients with high MRD levels had a median overall survival of 48.4 months vs. not reached for the intermediate and low levels. When examined by treatment arm, PFS and overall survival did not differ within each MRD category; however, treatment with FCR induced low levels of MRD more frequently than FC.